ABSTRACTRecent evidence suggested that muscle degeneration might lead and/or contribute to neurodegeneration, thus it possibly play a key role in the etiopathogenesis and progression of amyotrophic lateral sclerosis (ALS). To test this hypothesis, this study attempted to categorize functionally relevant genes within the genome-wide expression profile of human ALS skeletal muscle, using microarray technology and gene regulatory network analysis. The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls. The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals. In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism. Overall, the analytical approach used in this study offer the possibility to observe higher levels of correlation (i.e. common expression trends) among genes, whose function seems to be aberrantly activated during the progression of muscle atrophy.

pone-0057739-g004: Gene regulation networks.Graphical representation of the inter-gene connection existing in the ALS group (a) and controls (b). The correspondence between the numerical labels and the gene ontology annotation is displayed in table 3.

Mentions:
The graphical representation of the gene networks observed in the two experimental groups (figure 4), clearly showed that genes that were isolated in controls, formed a highly inter-connected sub-network in the ALS group. The correspondence between the numerical labels and the gene ontology annotation is displayed in table 3. For ALS patients, the AD of the network resulted to be 1.16. The network obtained from the normal group had many isolate nodes (83) and an AD as low as 0.2. The widest disease-related sub-network (formed by 22 genes) was mainly formed by mitochondrial genes, while the small sub-networks corresponded to ACTN3- and CHRNA1-correlated genes (figure 4, table 3).

pone-0057739-g004: Gene regulation networks.Graphical representation of the inter-gene connection existing in the ALS group (a) and controls (b). The correspondence between the numerical labels and the gene ontology annotation is displayed in table 3.

Mentions:
The graphical representation of the gene networks observed in the two experimental groups (figure 4), clearly showed that genes that were isolated in controls, formed a highly inter-connected sub-network in the ALS group. The correspondence between the numerical labels and the gene ontology annotation is displayed in table 3. For ALS patients, the AD of the network resulted to be 1.16. The network obtained from the normal group had many isolate nodes (83) and an AD as low as 0.2. The widest disease-related sub-network (formed by 22 genes) was mainly formed by mitochondrial genes, while the small sub-networks corresponded to ACTN3- and CHRNA1-correlated genes (figure 4, table 3).

Bottom Line:
The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls.The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals.In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism.

ABSTRACTRecent evidence suggested that muscle degeneration might lead and/or contribute to neurodegeneration, thus it possibly play a key role in the etiopathogenesis and progression of amyotrophic lateral sclerosis (ALS). To test this hypothesis, this study attempted to categorize functionally relevant genes within the genome-wide expression profile of human ALS skeletal muscle, using microarray technology and gene regulatory network analysis. The correlation network structures significantly change between patients and controls, indicating an increased inter-gene connection in patients compared to controls. The gene network observed in the ALS group seems to reflect the perturbation of muscle homeostasis and metabolic balance occurring in affected individuals. In particular, the network observed in the ALS muscles includes genes (PRKR1A, FOXO1, TRIM32, ACTN3, among others), whose functions connect the sarcomere integrity to mitochondrial oxidative metabolism. Overall, the analytical approach used in this study offer the possibility to observe higher levels of correlation (i.e. common expression trends) among genes, whose function seems to be aberrantly activated during the progression of muscle atrophy.